Peer Reviewed Publication , Clinical Pharmacology , First-in-Human

Dose Finding and Food Effect Studies of a Novel Abiraterone Acetate Formulation for Oral Suspension in Comparison to a Reference Formulation in Healthy Male Subjects

16 December 2021

Abstract: Currently approved formulations of the androgen synthesis inhibitor abiraterone acetate
(AA) consist of multiple tablets administered daily in a fasted state. Removing the food effect and
switching to a suspension formulation is expected to improve the pharmacokinetic profile and facilitate
drug administration for patients with late-stage prostate cancer. Two four-sequence, fourperiod
randomized crossover investigations were undertaken to establish the pharmacokinetic profiles
of single doses of commercially available Zytiga®, as the reference AA (R-AA), and a novel
tablet for oral suspension (TOS). Four single doses of TOS (from 62.5 to 250 mg) were compared in
study C01, and two single doses each of TOS (250 mg) and R-AA (1000 mg) were compared under
fasted and fed (modified fasted for R-AA) conditions in C02. Plasma concentrations of abiraterone
over time were measured, and pharmacokinetic parameters were calculated. Each doubling of the
dose of TOS was associated with a greater than 3-fold increase in exposure. A single dose of TOS
(250 mg) exhibited similar exposure over 24 h, whether given fasted (625 ng × h/mL) or fed (485 ng
× h/mL). A single dose of TOS (250 mg) was associated with higher (fasted, p = 0.028) or equivalent
exposure (fed) compared to 1000 mg R-AA fasted (532 ng × h/mL). Substantially higher exposures
were seen with 1000 mg R-AA under modified fasted conditions compared to TOS, irrespective of
prandial status (p < 0.001). TOS was generally safe and well tolerated in the study. A 250 mg dose
of a novel AA formulation for oral suspension demonstrated bioequivalence to 1000 mg R-AA under
fasted conditions. This novel TOS formulation also addresses some of the limitations of current AA treatment, including low bioavailability, high variability in systemic exposure and a large food effect. It may offer an alternative for patients with dysphagia or discomfort with swallowing large

16 December 2021